This story is part of The Salt Lake Tribune’s ongoing commitment to identify solutions to Utah’s biggest challenges through the work of the Innovation Lab.

When Bret Boyle attended medical school in California the symptoms of “the terrible triads” were drilled into his memory.

Night sweats, weight loss and lymphadenopathy (lymph node swelling) made up the three early signs of lymphoma, the catch-all term for cancers of the lymphatic system.

But when Boyle developed two of the three symptoms in 2014 — night sweats and weight loss — he wasn’t initially worried. His AC unit had broken during a hot summer and he’d expected to shed some pounds having recently decided to go vegan. Plus, he kept checking his lymph nodes and didn’t detect any swelling.

But after about six months, he began to worry. “It went on long enough that I realized, OK this is stupid,” Boyle said. “I’ve got to go at least get some blood work.”

After some insurance issues, Boyle got an appointment with his usual physician and the seriousness of the situation was immediately apparent. “When I saw him and told him the story I could see it in his eyes and I knew something was wrong,” Boyle recalled.

A few days later Boyle, then 56 years old, was diagnosed with mantle cell lymphoma — an extremely rare form of non-Hodgkin lymphoma.

“Blood cancers are typically the worst as far as being very insidious and difficult to diagnose,” Boyle said. He stopped working full time as a wound care specialist and went through chemotherapy and a stem cell transplant in 2015.

Boyle went into remission but within a year started having new, unexpected symptoms--including vision problems. The cancer seemed to be in his brain. “The best you can do is keep knocking it into remission and hope that it stays in remission for a long time before it comes back again,” Boyle said.

He and his wife Kerri left Salt Lake City and moved to Hawaii, but three years later his medication stopped working and symptoms returned. They moved back to Salt Lake City to access better care. That’s when Boyle went to the Huntsman Cancer Institute and was offered CAR-T cell therapy.

CAR stands for “chimeric antigen receptor.” CAR-T cell therapy essentially uses “cells as drugs to treat disease,” explained Dr. Daniel Couriel, medical director for the Center of Cellular Therapy and Regenerative Medicine at the Institute and Boyle’s care team.

With few other options, Boyle decided to go for it. “It’ll seek and destroy the cancer anywhere and everywhere in your body to include the brain,” he said. “Which was good for me because that’s the only place that it existed.”

CAR-T cell therapy has the potential to save lives, as it did for Boyle. But the production process, toxicity concerns and insurance challenges mean that not everyone who could benefit from the treatment can access, or afford it.

What is CAR-T cell therapy?

The therapy works by modifying the T cell, which physician and best-selling author Siddhartha Mukherjee describes as the “discerning cell,” in his book, “The Song of the Cell.” These cells work to detect and kill “virus-infected cells,” Mukherjee writes. However, cancers, he explains, “share some common features—among them, their invisibility to the immune system.”

In CAR-T cell therapy, T cells are modified to make the unseeable seen. A patient’s T cells are collected, then sent to a manufacturing lab where they are modified to produce a protein, the “chimeric antigen receptor” that allows the CAR-T cell “to specifically recognize certain types of tumor cells,” Couriel said.

This technology has been groundbreaking in the world of cancer treatment and research. Before 2017, the year the treatment received FDA approval, Couriel had nothing to offer patients like Boyle. “These are patients that would have died otherwise,” Couriel said. “So the comparison is no option.” And now I can offer them another line of treatment that offers the possibility of a 40% long term remission. It’s wonderful.”

However, while the results of CAR-T cell therapy can seem miraculous, risk for recurrence still exists. “There’s still a substantial number of patients that will recur with their cancer,” Couriel said. There’s still a substantial number of patients that will recur with their cancer,” Couriel said. “Another focus is to make these CAR-T cells persist in the patients so the tumor doesn’t come back.”

In spite of its promise, CAR-T therapy remains inaccessible for many. Demand outstrips supply and there are thousands more patients that could benefit from CAR-T therapy than receive it each year. There are three reasons for that, according to Couriel.

First, the manufacturing process isn’t currently scalable. The Huntsman Cancer Institute purchased a machine dubbed “Prodigy,” which produces CAR-T cells, but its production capacity is limited. Second, the treatment can be prohibitively expensive (sometimes upward of $400,000) and, as in Boyle’s case, it can be a battle to get insurance coverage. Finally, there are relatively few centers equipped to help patients deal with the side effects, especially “neurotoxicity.”

In the worst case scenarios, that toxicity can result in seizures and comas. After receiving treatment patients must be closely monitored for several weeks, and to be hospitalized quickly if necessary. That is an extra burden for patients who live in remote locations from highly specialized cancer care.

Shrinking the divide for those who need care

Dr. Nausheen Ahmed learned about the intricacies of CAR-T cell therapy during a transplant and cell therapy fellowship at Case Western University. “The science is just pretty impressive,” Ahmed said. “You can take cells that naturally exist, genetically modify them and now they’re your weapon against cancer.”

Now an assistant professor at the University of Kansas’ Division of Hematologic Malignancies and Cellular Therapeutics, Ahmed researched the inequalities in who gets treated with CAR-T cell therapy and found significant disparities across ethnic and socioeconomic groups.

“Patients that may be in lower socioeconomic groups may not have as much access,” she said. “They may not have insurance that covers it.”

While receiving the therapy, patients must stay near their care facility to monitor toxicity levels. So patients need a 24/7 caregiver and a place to stay -- two requirements that insurance may not cover.

The University of Utah can provide housing for patients and families who travel there for care, but according to the program’s webpage monthly rates start at about $1,000 per month.

Research to shorten the period of time it takes to manufacture CAR-T cells is ongoing. There are novel CAR-T manufacturing processes that might take just two or three days rather than the current standard of two to eight weeks.

Kansas researcher Ahmed said trials with “allogeneic constructs,” that is, modified cells that don’t come from the patient, but from a healthy donor, are in the works. This could potentially lead to the manufacture of CAR-T cells that could be “kept on the shelf,” thus solving the challenge of the lengthy manufacturing wait time.

“Those things are on the scientific edge,” Ahmed explained. “I’m seeing CAR-T cell therapies for solid tumors in clinical trials. I’ve seen breast cancer patients, colon cancer patients and liver cancer patients that I’m treating with CAR-T.”

The Huntsman’s Couriel calls the therapy “the tip of the iceberg. You are witnessing the very beginning of a new era in oncology.”

In March, Bret Boyle will mark two years since he received CAR-T cell therapy. “Most chemo drugs do not cross what’s called the blood brain barrier,” he said. “Fortunately, for me, CAR-T does. It saved my life.” He’s now going back to work — this time for a skilled nursing facility’s wound care outreach program.

“I’m going back to a specialty that I know and love,” he said.